The human intestine is thought to be sterile in utero, but it is exposed to a large variety of maternal and environmental microbes immediately after birth. Thereafter, a dynamic period of microbial colonization and succession occurs, which is influenced by factors such as delivery mode, environment, diet and host genotype, all of which impact upon the composition of the gut microbiota, particularly during early life. Subsequently, the microbiota stabilizes and becomes adult-like [1]. The human gut microbiota contains more than 1500 different phylotypes dominated in abundance levels by two major bacterial divisions (phyla), the Bacteroidetes and the Firmicutes [2-3]. The successful symbiotic relationships arising from bacterial colonization of the human gut have yielded a wide variety of metabolic, structural, protective and other beneficial functions. The enhanced metabolic activities of the colonized gut ensure that otherwise indigestible dietary components are degraded with release of by-products providing an important nutrient source for the host and additional health benefits. Similarly, the immunological importance of the gut microbiota is well-recognized and is exemplified in germfree animals which have an impaired immune system that is functionally reconstituted following the introduction of commensal bacteria [4-6].
Dramatic changes in microbiota composition have been documented in gastrointestinal disorders such as inflammatory bowel disease (IBD). For example, the levels of Clostridium cluster XIVa and Clostridium cluster XI (F. prausnitzii) bacteria are reduced in IBD patients whilst numbers of E. coli are increased, suggesting a shift in the balance of symbionts and pathobionts within the gut [7-11].
In recognition of the potential positive effect that certain bacterial strains may have on the animal gut, various strains have been proposed for use in the treatment of various diseases (see, for example, [12-15]). A number of strains, including mostly Lactobacillus and Bifidobacterium strains, have been proposed for use in treating various bowel disorders (see [16] for a review). Strains of the genus Blautia have also been proposed for use in modulating the microbial balance of the digestive ecosystem in IBS patients (WO 01/85187). However, the relationship between different bacterial strains and different diseases, and the precise effects of particular bacterial strains on the gut and at a systemic level and on any particular types of diseases, are poorly characterised.
There is a requirement for the potential effects of gut bacteria to be characterised so that new therapies using gut bacteria can be developed.
US 2010/0247489 describes the use of mineral nutrients to treat digestive disorders. US′789 proposes optionally also using numerous different genera of bacteria, including Enterobacteriaceae, to prevent and reduce gas formation in the colon, so this document suggests that increasing Enterobacteriaceae spp. in the gastrointestinal tract may be employed to treat certain diseases. U.S. '789 does not discuss any methods for reducing Enterobacteriaceae spp.
WO 2016/086206 suggests that bacteria in the order Clostridiales, including Enterbacteriaceace spp., can be used to treat or prevent dysbiosis. There is no suggestion in WO′206 that reducing the level of Enterobacteriaceace spp. in the gastrointestinal tract can be used to treat diseases, nor any suggestion regarding how a reduction in the level of Enterbacteriaceace spp. might be achieved.
WO 2012/142605 proposes that it may be possible to treat a number of different diseases with a combination of microorganisms. WO′605 suggests a large number of possible bacterial species that could be employed, but there is no teaching in WO′605 as to how any of the proposed bacterial species could be used to treat any of the diseases proposed.